According to epidemiological data, breast cancer is the most frequent form of cancer in women [1]. Particularly aggressive breast cancers are characterized by invasive and metastatic behavior [2]. The treatment of such aggressive breast cancers is extremely problematic and very costly due to the use of specific antibodies, which are employed only after multiple positive histochemical tests [3].
The cause for the aggressive qualities of the tumors lies in the overexpression of cell membrane-bound receptors [4]. The action of these receptors is overexpression with uncontrolled stimulation of cell proliferation and inhibition of controlled cell death, or apoptosis [5, 6].
The uncontrolled cell proliferation results in rapid tumor growth. It is particularly critical when apoptosis of the aggressive tumor cells is suppressed at the same time [2].
The survival prognosis of such breast cancer diseases is extremely low [3]. Treatment with the antibody trastuzumab is not only very costly, but also fails when the HER2 receptor, to which trastuzumab binds, has been degenerated as a result of mutations. The receptor is then constitutively active and cannot be inhibited by the antibody [3, 4].
According to recent findings, a second factor plays another important role in aggressive breast cancers. This is the enzyme Brk, which is overexpressed in the aggressive tumor cells like HER2 [2, 4, 7]. The activity of HER2 is amplified further by Brk [2, 7]. Brk thus not only amplifies the uncontrolled growth of the tumor cells, but also inhibits the apoptosis of the same [2,8-11]. The aggressiveness of the tumor cells is further increased by Brk in that the formation of metastases is amplified [2]. This is a consequence of the fact that the tumor cells do not die off after detaching from the tumor cell group and a separate tumor cell group is formed [2].
The only possible treatment of such aggressive breast cancers is with inhibitors. A previously used HER2 inhibitor called lapatinib, however, shows effects only in a limited number of cases [4]. Failure of the inhibitor therapies conducted until now has been blamed on tumor cell resistances, which are a result of mutations of HER2, among other things. An inhibitor against Brk and HER2 is not known to date.